Phase II study of gefitinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) gene mutations detected by PNA-LNA PCR clamp

Abstract

7076 Background: The responsiveness to gefitinib has been reported to closely link to the presence of EGFR gene mutations. We developed a method, PNA-LNA PCR clamp, capable of detecting EGFR mutations in the presence of 100-fold background of wild type EGFR from normal cells (Can Res. 2005;65:7276). This study was prospectively designed to evaluate 1) the sensitivity and the specificity of the PNA-LNA PCR clamp (sample size > 100 pts) and 2) a phase II study of gefitinib for NSCLC patients (pts) with EGFR gene mutations (sample size > 25 pts to show the lower limit of 95% CI > 50%). Methods: Clinical samples (sputum, pleural effusion, bronchial fluid and paraffin tissue) were obtained from consecutive NSCLC pts with informed consent in our institution, and were tested by the PNA-LNA PCR clamp. After the second informed consent, for PS 0–2, inoperable stage III and IV pts with EGFR mutations, gefitinib (250mg P.O. daily) was given as the second treatment after docetaxel containing chemotherapy. In case of poor PS pts, the first line chemotherapy was omitted. Results: From Sept. ’04 to Oct. ’05, samples from 100 of a total of 107 pts were informative of EGFR mutation status. PNA-LNA PCR clamp detected EGFR mutations in 38 pts (38%) (15 males/23 females; median age:62; adenoca.:33 pts). Exon 19 deletions, L858R and L861Q were found in 25 (66%), 12 (32%) and 1 (2%) patients, respectively. But 62 pts (51 males/11 females; median age:66; Ad:43 pts) were judged to have wild type EGFR. Between positive and negative pts in EGFR mutation, there was significant difference in the distinction of sex (p = 0.00001). Gefitinib was given to 26 pts with EGFR mutations as the first line (4 pts) or the second line treatment (22 pts). One patient and 20 patients showed CR and PRs, respectively, and the response rate was 81% (95% CI: 61–94%). For patients with wild EGFR genes, gefitinib was given to 5 patients and one patient (20%) showed PR. The response rate was significantly different between wild and mutant EGFR genes detected by the PNA-LNA PCR clamp (p = 0.017). Conclusions: PNA-LNA PCR clamp could reliably detect EGFR mutations, indicating the method is useful to detect EGFR mutations in clinical specimens. Updated data will be presented at the meeting. No significant financial relationships to disclose.